Role of the Wilms' tumor suppressor gene Wt1 in pancreatic development

• Published in: Developmental dynamics 2018-07, Vol.247 (7), p.924-933
• Main Authors: Ariza, Laura, Cañete, Ana, Rojas, Anabel, Muñoz‐Chápuli, Ramón, Carmona, Rita
• Format: Article
• Language: English
• Subjects: Acinar cells; Cell proliferation; Clonal deletion; Embryos; Endothelial cells; epithelial–mesenchymal transition; intestinal rotation; Intestine; Liver; Localization; Mesenchyme; Mesentery; Mesothelium; Organs; Pancreas; pancreatic stellate cells; pancreatic stroma; Stellate cells; Tumor suppressor genes; Tumors; Wilms' tumor
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24636

The Wilms tumor suppressor gene (Wt1) encodes a transcription factor involved in the development of a number of organs, but the role played by Wt1 in pancreatic development is unknown. The pancreas contains a population of pancreatic stellate cells (PSC) very important for pancreatic physiology. We described elsewhere that hepatic stellate cells originate from the WT1‐expressing liver mesothelium. Thus, we checked if the origin of PSCs was similar. WT1 expression is restricted to the pancreatic mesothelium. Between embryonic day (E) 10.5 and E15.5, this mesothelium gives rise to mesenchymal cells that contribute to a major part of the PSC and other cell types including endothelial cells. Most WT1 systemic mutants show abnormal localization of the dorsal pancreas within the mesentery and intestinal malrotation by E14.0. Embryos with conditional deletion of WT1 between E9.5 and E12.5 showed normal dorsal pancreatic bud and intestine, but the number of acini in the ventral bud was reduced approximately 30% by E16.5. Proliferation of acinar cells was reduced in WT1 systemic mutants, but pancreatic differentiation was not impaired. Thus, mesothelial‐derived cells constitute an important subpopulation of pancreatic mesodermal cells. WT1 expression is not essential for pancreas development, although it influences intestinal rotation and correct localization of the dorsal pancreas within the mesogastrium. Developmental Dynamics 247:924–933, 2018. © 2018 Wiley Periodicals, Inc. Key Findings By midgestation, the pancreatic mesothelium expresses WT1 and gives rise to mesenchymal cells that contribute to a major part of the pancreatic stellate cells and other cell types including endothelial cells. An abnormal localization of the dorsal pancreas within the mesentery and intestinal malrotation are observed in WT1 systemic mutants. Proliferation of acinar cells was reduced in WT1 systemic mutants, but pancreatic differentiation was not impaired. WT1 expression is dispensable for pancreas development, although it influences intestinal rotation and correct localization of the dorsal pancreas within the mesogastrium.